sulopenem etzadroxil/probenecid (Pending FDA Approval)

Action and Spectrum

Actions and spectrum: 

sulopenem etzadroxil/probenecid is a combination antibiotic medication that has a broad spectrum of activity against various gram-negative and gram-positive bacteria. sulopenem, the active ingredient, is a penem beta-lactam antibiotic that inhibits bacterial cell wall synthesis.

Etzadroxil and probenecid enhance the activity of sulopenem by increasing its bioavailability and prolonging its half-life. This is used for the treatment of urinary tract infections, including complicated infections caused by multidrug-resistant bacteria. 

Drug Interaction

Adverse Reaction

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity to any component of the product, penicillins, cephalosporins, or other beta-lactams. 
• History of severe hypersensitivity (e.g., anaphylaxis) to beta-lactam antibacterial drugs. 
• Patients with renal impairment (creatinine clearance less than 50 mL/min) who are taking concomitant drugs that inhibit renal tubular secretion because of the potential for increased plasma levels of sulopenem.

Caution: 

sulopenem-etzadroxil/probenecid should be used with caution in patients with a history of allergic reactions to beta-lactams, cephalosporins, or penicillins, as they may also be allergic to this medication. It should be used under caution in patients with impaired renal function, as it can lead to increased levels of probenecid and its metabolites in the blood. It may also interact with other medications that are eliminated by the kidneys, so caution should be exercised when used in combination with these drugs.  

Comorbidities: 

The comorbidities that may affect the use of sulopenem etzadroxil/probenecid are not well established. However, caution should be exercised when using the drug in patients with a history of hypersensitivity or serious adverse reactions to penicillins or other beta-lactams, as well as those with impaired renal function. 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

sulopenem is a new beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Etzadroxil is an ester prodrug of the active moiety, the broad-spectrum cephalosporin antibiotic etzadronic acid. Probenecid, on the other hand, is a uricosuric agent that increases the urinary excretion of uric acid by inhibiting its reabsorption. This drug combination works by inhibiting the breakdown of sulopenem and increasing its plasma concentrations, thus enhancing its antibacterial activity. Probenecid also reduces the renal clearance of etzadroxil, prolonging its half-life and increasing its systemic exposure.  

Pharmacodynamics: 

sulopenem etzadroxil/probenecid is a combination antibiotic that contains sulopenem, an orally active penem antibiotic, and probenecid, a uricosuric agent. sulopenem inhibits bacterial cell wall synthesis by binding to and inhibiting penicillin-binding proteins (PBPs), while probenecid blocks the renal tubular reabsorption of uric acid. This combination extends the antibacterial spectrum of sulopenem, enhances its activity against Gram-negative bacteria, and increases its oral bioavailability by reducing renal excretion.  

Pharmacokinetics: 

Absorption 

After oral administration, the etzadroxil/probenecid component of the drug is rapidly absorbed from the gastrointestinal tract, while sulopenem has low oral bioavailability. The presence of probenecid in the formulation enhances the absorption of etzadroxil by inhibiting its renal excretion. 

Distribution 

sulopenem has a volume of distribution of approximately 17-21 L, while the distribution of etzadroxil/probenecid is not well characterized. Both drugs are expected to distribute to various body tissues and fluids. 

Metabolism 

sulopenem is primarily metabolized in the liver via hydrolysis and oxidation, while etzadroxil is rapidly hydrolyzed to cefadroxil, which is further metabolized to inactive compounds. Probenecid is not metabolized but acts as a renal tubular inhibitor, increasing the plasma concentrations of etzadroxil and cefadroxil. 

Elimination and excretion 

sulopenem and its metabolites are eliminated mainly via the urine (about 50% unchanged), with a half-life of approximately 3-4 hours. Etzadroxil and its metabolite cefadroxil are excreted primarily in the urine, with a half-life of about 1.5 hours. Probenecid has a half-life of about 6 hours and is eliminated renally via active tubular secretion and glomerular filtration. 

Adminstartion

Administration: 

sulopenem etzadroxil/probenecid is an oral tablet that should be taken by mouth, usually twice daily. It can be taken with or without food. The tablets should be administered whole with a full glass of water. It is important to follow the dosage and administration instructions provided by the healthcare provider or on the prescription label. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sulopenem etzadroxil/probenecid 

Pronounced: sul-open-em et-zuh-drox-il/proh-ben-uh-sid  

Why do we use sulopenem etzadroxil/probenecid? 

sulopenem etzadroxil/probenecid is a combination antibiotic used for the treatment of uncomplicated urinary tract infections caused by susceptible bacteria. It is used for the treatment of complicated urinary tract infections, including pyelonephritis, caused by susceptible bacteria in patients who have limited or no alternative treatment options.